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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SNAPC4
small nuclear RNA activating complex polypeptide 4
Chromosome 9 Β· 9q34.3
NCBI Gene: 6621Ensembl: ENSG00000165684.7HGNC: HGNC:11137UniProt: Q5SXM2
43PubMed Papers
21Diseases
0Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
snRNA transcription by RNA polymerase IIIsnRNA-activating protein complexRNA polymerase III general transcription initiation factor activityDNA bindingneurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionneurodegenerative diseaseCrohn's diseaseasthma
✦AI Summary

SNAPC4 is a critical component of the snRNA-activating protein complex (SNAPc), which regulates transcription of small nuclear RNA genes required for RNA processing 1. As a DNA-binding subunit of SNAPc, SNAPC4 recognizes the proximal sequence element in snRNA promoters and recruits transcription factors essential for both RNA polymerase II and III-dependent snRNA transcription 2. The protein's function is evolutionarily conserved across eukaryotes 2, and its activity is regulated through SUMOylation, which is necessary for proper SNAPc complex assembly and snRNA transcriptional activity 3. Bi-allelic SNAPC4 variants cause autosomal recessive neurodevelopmental disorder characterized by developmental regression, progressive spastic paraparesis, and oromotor dysfunction 1. Loss of SNAPC4 function leads to decreased snRNA expression and global dysregulation of alternative splicing, impairing the spliceosome's ability to process transcripts 1. Beyond neurological disease, genetic variants in SNAPC4 have been associated with ankylosing spondylitis susceptibility in multiple populations 45, and shared genetic overlap with inflammatory bowel disease and iridocyclitis 6. SNAPC4 dysfunction represents a previously unrecognized mechanism disrupting splicing-dependent cellular processes critical for neurological development and immune homeostasis.

Sources cited
1
SNAPC4 is a SNAPc subunit critical for DNA binding; bi-allelic variants cause neurodevelopmental disorder with motor regression and spastic paraparesis through loss of function, decreased snRNA expression, and global dysregulation of alternative splicing
PMID: 36965478
2
SNAPC4 is conserved across eukaryotes as a SNAPc subunit involved in snRNA gene transcription, binds snRNA promoters, and is essential for gametophyte and zygote development
PMID: 33693812
3
SNAPC4 SUMOylation is required for proper snRNA transcription and assembly of the SNAPc complex
PMID: 40956881
4
SNAPC4 rs11145835 variant is associated with increased risk of ankylosing spondylitis in Chinese Han population and correlates with decreased SNAPC4 expression
PMID: 24334645
5
SNAPC4 variants have been investigated for association with ankylosing spondylitis pathogenesis in genome-wide association studies
PMID: 26590821
6
SNAPC4 is among shared genetic overlap genes between inflammatory bowel disease and iridocyclitis
PMID: 39472800
7
SNAPC4 variants were identified in prenatal exome reanalysis associated with human disease
PMID: 40186013
Disease Associationsβ“˜21
neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionOpen Targets
0.68Moderate
neurodegenerative diseaseOpen Targets
0.44Moderate
Crohn's diseaseOpen Targets
0.33Weak
asthmaOpen Targets
0.28Weak
inflammatory bowel diseaseOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
IGA glomerulonephritisOpen Targets
0.18Weak
colitisOpen Targets
0.14Weak
enteritisOpen Targets
0.12Weak
ulcerative colitisOpen Targets
0.09Suggestive
early-onset non-syndromic cataractOpen Targets
0.08Suggestive
ankylosing spondylitisOpen Targets
0.07Suggestive
Total congenital cataractOpen Targets
0.07Suggestive
Cataract-microcornea syndromeOpen Targets
0.07Suggestive
Partial congenital cataractOpen Targets
0.07Suggestive
psoriasisOpen Targets
0.07Suggestive
sclerosing cholangitisOpen Targets
0.07Suggestive
early-onset nuclear cataractOpen Targets
0.06Suggestive
Cataract with Y-shaped suture opacitiesOpen Targets
0.06Suggestive
Posterior polar cataractOpen Targets
0.06Suggestive
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionUniProt
Pathogenic Variants11
NM_003086.4(SNAPC4):c.2499+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_003086.4(SNAPC4):c.810+1G>ALikely pathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜…β˜†β˜†β˜†2025
NM_003086.4(SNAPC4):c.1484G>A (p.Trp495Ter)Likely pathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜…β˜†β˜†β˜†2024β†’ Residue 495
NM_003086.4(SNAPC4):c.1500+1G>ALikely pathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜…β˜†β˜†β˜†2024
NM_003086.4(SNAPC4):c.2527+1G>ALikely pathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜…β˜†β˜†β˜†2023
NM_003086.4(SNAPC4):c.1157A>G (p.Gln386Arg)Pathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜†β˜†β˜†β˜†2023β†’ Residue 386
NM_003086.4(SNAPC4):c.1321G>A (p.Asp441Asn)Pathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜†β˜†β˜†β˜†2023β†’ Residue 441
NM_003086.4(SNAPC4):c.2428C>T (p.Arg810Ter)Pathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜†β˜†β˜†β˜†2023β†’ Residue 810
NM_003086.4(SNAPC4):c.737+5G>TPathogenic
Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
β˜†β˜†β˜†β˜†2023
NM_003086.4(SNAPC4):c.1436T>C (p.Ile479Thr)Pathogenic
SNAPC4 related condition
β˜†β˜†β˜†β˜†2023β†’ Residue 479
NM_003086.4(SNAPC4):c.472-2_472-1delPathogenic
SNAPC4 related condition
β˜†β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
POLR3DProtein interaction100%TBPProtein interaction99%GTF2A1Protein interaction97%GTF2A2Protein interaction97%POU2F1Protein interaction97%GTF2BProtein interaction96%
Tissue Expression6 tissues
Liver
100%
Ovary
83%
Bone Marrow
74%
Lung
64%
Brain
31%
Heart
23%
Gene Interaction Network
Click a node to explore
SNAPC4POLR3DTBPGTF2A1GTF2A2POU2F1GTF2B
PROTEIN STRUCTURE
Preparing viewer…
PDB7ZWD Β· 3.00 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.99LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.85 [0.73–0.99]
RankingsWhere SNAPC4 stands among ~20K protein-coding genes
  • #9,788of 20,598
    Most Researched43
  • #2,790of 5,498
    Most Pathogenic Variants11
  • #9,580of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedSNAPC4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Bi-allelic SNAPC4 variants dysregulate global alternative splicing and lead to neuroregression and progressive spastic paraparesis.
PMID: 36965478
Am J Hum Genet Β· 2023
1.00
2
Determination of IL1 R2, ANTXR2, CARD9, and SNAPC4 single nucleotide polymorphisms in Iranian patients with ankylosing spondylitis.
PMID: 26590821
Rheumatol Int Β· 2016
0.90
3
Multiregion exome sequencing indicates a monoclonal origin of esophageal spindle-cell squamous cell carcinoma.
PMID: 39022845
J Pathol Β· 2024
0.80
4
Functional and evolutionary analysis of the Arabidopsis 4R-MYB protein SNAPc4 as part of the SNAP complex.
PMID: 33693812
Plant Physiol Β· 2021
0.70
5
SUMO conjugation to promoter-proximal sequence elements-associated proteins impacts on snRNA transcription.
PMID: 40956881
Proc Natl Acad Sci U S A Β· 2025
0.60